Rule-selection operates during behaviors of different degrees of abstractness and complexity in humans and animals. Rule-selection is defined as the process by which a previously learned rule re-acquires the ability to control behavior. Thus, successful performance on alternating tasks requires selection of rules that guide task-appropriate behavior. A recent theory proposes that in primate's prefrontal cortex (PF) and the striatum (STR) are a cooperative system that selects behavior-guiding rules. Neurons in the monkey PF show rule-dependent activity that is selective for one rule but not for another. In rats the PF, particularly the medial PF, may be involved in rule-shifting behavior. Interdependence of function between PF and STR suggests that PF and STR may also work as a system in selecting task appropriate rules in rats. Moreover, functionally distinctive sub-regions within PF and STR may sub-serve different aspects in rule-selection and may contribute differential behavioral deficits following damage to these sub-regions. This proposal advocates a rodent model to investigate the mechanisms involved in the rule-selection process. Using an integrative behavioral and neurophysiological approach, in conjunction with lesion and pharmacological manipulations, the proposed experiments examine three issues: what type of rule-related information is processed within the PF and STR while the rat adapts to context-appropriate rules; whether a differential contribution is made by sub-regions of PF and STR; and how dopamine affects this information within PF and STR. The behavioral task in the proposed experiments requires rats to lever press for food while under the control of one of two rules, conditional (color) and spatial (location). Neurons in rat PF and/or STR might show rule-dependent activity, which reflects a rule-selection process. Properties of PF and STR neurons might differ during alternation of rules. Consequently, the precise contribution of mPF and STR to rule-selection may differ. Dopamine may contribute in situations where established associations are no longer valid, and maintain the optimal function of the PF-STR system. Disrupting prefrontal and striatal function, either by lesions (reversible and irreversible) or by altering dopamine transmission via infusions of dopamine agonists and antagonists into PF and STR, is expected to disrupt rule-related processes, thereby disrupting subsequent behavior.